A new study has come up empty-handed after pursuing a genetic explanation for why one identical twin developed multiple sclerosis while the other stayed healthy.
Researchers transcribed the complete genetic blueprints for a pair of identical twins, looking for differences that might explain why one has multiple sclerosis and the other does not. No trace of what caused the discrepancy appeared in the twins’ DNA. And scientists found no smoking gun when they compared levels of gene activity between the sick and well twin. The results appear in a report published April 29 in Nature.
“We looked under a lot of rocks and we found no differences that we could replicate,” says Stephen Kingsmore, a geneticist at the National Center for Genome Resources in Santa Fe, N.M., and leader of the new study. The finding “points to some novel environmental trigger that must be very important to the disease. We don’t know what it is.”
But the new study is small; it examines only three pairs of twins and one type of immune cell known to be involved in multiple sclerosis. A telling difference between sickness and health might be found in other types of cells, such as immune cells called B cells or in oligodendrocytes, which are cells that make the nerve cell insulation called myelin, says Esteban Ballestar of the Bellvitge Biomedical Research Institute in Barcelona, Spain. “They are closing a door here, but I think, perhaps, the door should be open,” he says.
In multiple sclerosis the immune system attacks and damages the myelin sheath that helps speed electrical communication between nerves, the equivalent of scraping the coating away from an electrical wire. The damage results in pain and symptoms such as loss of coordination and vision.
In the new study, Kingsmore and his colleagues determined the entire genetic makeup of immune cells called T cells from a pair of female twins. One of the women developed multiple sclerosis at age 30 while her twin remained healthy. The twins are now old enough that the healthy one is not likely to develop the disease.
Identical twins share the same genetic makeup, and the researchers confirmed that both women carried variants of genes already known to increase the risk of getting multiple sclerosis. Scientists had thought that maybe the sick twin had developed an additional mutation in her DNA that finally triggered the disease. But the team found no such mutations.
Another way to rev up the immune system and induce it to attack the body is to increase the activity of certain genes. Upping gene activity doesn’t necessarily involve changing the genes themselves, but can be done by altering chemical tags on the DNA. In two pairs of twins, the team examined more than 2 million DNA locations that had been tagged with a common label, known as a methyl group, that keeps gene activity in check.
In a previous study, Ballestar’s group found lower levels of methylated DNA when they compared people with lupus (SN: 1/16/2010, p.13) to their healthy identical twins. But Kingsmore and his colleagues found no similar differences that could account for just one twin developing MS.
The team also measured gene activity in three sets of identical twins, including the sisters who had their genomes sequenced. The researchers did find some minor differences, but none could explain why one twin got sick and the other didn’t.